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首页> 外文期刊>AIDS Research and Human Retroviruses >Genotypic susceptibility scores and HIV type 1 RNA responses in treatment-experienced subjects with HIV type 1 infection.
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Genotypic susceptibility scores and HIV type 1 RNA responses in treatment-experienced subjects with HIV type 1 infection.

机译：在治疗经验丰富的1型HIV感染者中，基因型易感性评分和1型HIV RNA反应。

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This study compared the role of genotypic susceptibility scores (GSS) as a predictor of virologic response in a group (n = 234) of HIV-infected, protease inhibitor (PI)-experienced subjects. Two scoring methods [discrete genotypic susceptibility score (dGSS) and continuous genotypic susceptibility score (cGSS)] were developed. Each drug in the subject's regimen was given a binary susceptibility score using Stanford inferred drug resistance scores to calculate the dGSS. In contrast to the dGSS, the cGSS model was designed to reflect partial susceptibility to a drug. Both GSS were independent predictors of week 16 virologic response. We also compared the GSS to a phenotypic susceptibility score (PSS) model on a subset of subjects that had both GSS and PSS performed, and found that both models were predictive of virologic response. Genotypic analyses at enrollment showed that subjects who were virologic nonresponders at week 16 revealed enrichment of several mutated codons associated with nucleoside reverse transcriptase inhibitors (NRTI) (codons 67, 69, 70, 118, 215, and 219) or PI resistance (codons 10, 24, 71, 73, and 88) compared to subjects who were virologic responders. Regression analyses revealed that protease mutations at codons 24 and 90 were most predictive of poor virologic response, whereas mutations at 82 were associated with enhanced virologic response. Certain NNRTI-associated mutations, such as K103N, were rapidly selected in the absence of NRTIs. These data indicate that GSS may be a useful tool in selecting drug regimens in HIV-1-infected subjects to maximize virologic response and improve treatment outcomes.
机译：这项研究比较了基因型易感性评分（GSS）作为一组HIV感染，蛋白酶抑制剂（PI）感染者的病毒学应答预测指标（n = 234）的作用。制定了两种评分方法[离散基因型药敏分数（dGSS）和连续基因型药敏分数（cGSS）]。使用Stanford推断的耐药性评分来计算dGSS，对受试者方案中的每种药物给予二元敏感性评分。与dGSS相比，cGSS模型旨在反映对药物的部分敏感性。两个GSS都是第16周病毒学应答的独立预测因子。我们还对同时进行了GSS和PSS的一部分受试者的表型易感性评分（PSS）模型进行了GSS的比较，发现这两种模型都可以预测病毒学应答。入选时的基因型分析表明，在第16周对病毒学无反应的受试者显示与核苷逆转录酶抑制剂（NRTI）（67、69、70、118、215和219号密码子）或PI抵抗（10号密码子）相关的几个突变密码子的富集。 ，24、71、73和88）与病毒学应答者比较。回归分析显示，密码子24和90处的蛋白酶突变最能预测不良的病毒学应答，而82处的突变与增强的病毒学应答有关。在不存在NRTI的情况下，可以快速选择某些与NNRTI相关的突变，例如K103N。这些数据表明，GSS可能是在HIV-1感染的受试者中选择药物治疗方案以最大化病毒学应答和改善治疗效果的有用工具。

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